Cardiovascular and Renal Microvascular Outcome Study With Linagliptin in Patients With Type 2 Diabetes Mellitus (CARMELINA)
Verified February 2015 by Boehringer Ingelheim
Eli Lilly and Company
Information provided by (Responsible Party):
First received: July 9, 2013
Last updated: February 20, 2015
Last verified: February 2015
The aim of the study is to investigate the longterm impact on cardiovascular morbidity, mortality and renal function of treatment with linagliptin in a selected population of patients with T2DM and to compare outcomes against placebo, on a background of standard of care.
Diabetes Mellitus, Type 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
||CARMELINA: A Multicenter, International, Randomized, Parallel Group, Double-blind, Placebo-controlled, Cardiovascular Safety and Renal Microvascular Outcome Study With Linagliptin, 5 mg Once Daily in Patients With Type 2 Diabetes Mellitus at High Vascular Risk
Primary Outcome Measures:
- Time to the first occurence of any of the following adjudicated components of the primary composite endpoint: cardiovascular death, non fatal myocardial infarction, non fatal stroke and hospitalization for unstable angina pectoris [ Time Frame: 48 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Time to first occurence of any of the following adjudicated components: cardiovascular death, non fatal myocardial infarction and non fatal stroke [ Time Frame: 48 months ] [ Designated as safety issue: No ]
- Time to first occurence of any of the following adjudicated composite renal endpoint: renal death, end stage renal disease and a sustained decrease of 50% or more in estimated glomerular filtration rate [ Time Frame: 48 months ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||January 2018 (Final data collection date for primary outcome measure)
Placebo Comparator: Placebo
placebo matching tablets
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Documented diagnosis of T2DM before visit 1(screening).
- Male or female patients who are drug-naïve or pre-treated with any antidiabetic background medication, excluding treatment with GLP-1 receptor agonists, DPP-4 inhibitors or SGLT-2 inhibitors if => consecutive 7 days.
- Stable antidiabetic background medication (unchanged daily dose) for at least 8 weeks prior to randomization. If insulin is part of the background therapy, the average daily insulin dose should not have changed by more than 10% within the 8 weeks prior to randomization compared with the daily insulin dose at randomization.
- HbA1c of => 6.5% and <= 10.0% at Visit 1 (screening)
- Age => 18 years at Visit 1(screening). For Japan only: Age => 20 years at Visit 1
- Body Mass Index (BMI) <= 45 kg/m2 at Visit 1 (screening)
- Signed and dated written informed consent by date of Visit 1(screening) in accordance with Good Clinical Practice (GCP) and local legislation prior to any study related procedure
- High risk of CV events defined by: 1) albuminuria (micro or macro) and previous macrovascular disease and/or 2) impaired renal function with predefined UACR
- Type 1 diabetes mellitus.
- Treatment (=> 7 consecutive days) with GLP-1 receptor agonists, other DPP-4 inhibitors or SGLT-2 inhibitors prior to informed consent. Note: This also includes clinical trials where these antidiabetic drugs have been provided to the patient.
- Active liver disease or impaired hepatic function, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase (AP) => 3 x upper limit of normal (ULN) as determined at Visit 1.
- eGFR <15 ml/min (severe renal impairment or ESRD, MDRD formula), as determined during screening at Visit 1 and/or the need for maintenance dialysis.
- Any previous (or planned within next 12 months) bariatric surgery (open or laparoscopic) or intervention (gastric sleeve).
- Pre-planned coronary artery re-vascularisation (PCI, CABG) or any previous PCI and/or CABG <= 2 months prior informed consent.
- Known hypersensitivity or allergy to the investigational products or its excipients.
- Any previous or current alcohol or drug abuse that would interfere with trial participation in the opinion of the investigator.
- Participation in another trial with an investigational drug ongoing or within 2 months prior to visit 1 (screening).
- Pre-menopausal women (last menstruation = 1 year prior to informed consent) who are nursing or pregnant, are of child-bearing potential and are not practicing an acceptable method of birth control (acceptable methods of birth control include tubal ligation, transdermal patch, intra uterine devices/systems (IUDs/IUSs), oral, implantable or injectable contraceptives, sexual abstinence (if allowed by local authorities), double barrier method and vasectomised partner) or do not plan to continue using acceptable method of birth control throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial.
- Patients considered unreliable by the investigator concerning the requirements for follow up during the study and/or compliance with study drug administration, have a life expectancy less than 5 years for non-CV causes, or have cancer other than non-melanomaskin cancer within last 3 years, or has any other condition than mentioned which in the opinion of the investigator, would not allow safe participation in the study.
- Acute coronary syndrome (ACS), diagnosed <= 2 months prior to visit 1 (screening).
- Stroke or TIA <= 3 months prior to visit 1 (screening).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01897532
Eli Lilly and Company
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||July 9, 2013
||February 20, 2015
||Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
China: China Food and Drug Administration (CFDA)
Croatia: Ministry of Health and Social Care
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Malaysia: Ministry of Health
Mexico: Federal Commission for Sanitary Risks Protection
Netherlands: Central Committee Research Involving Human Subjects
Poland: Registration Medicinal Product Medical Device Biocidal Product
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health and Social Development Russian Federation
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Taiwan : Food and Drug Administration
Ukraine: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on February 27, 2015
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Dipeptidyl-Peptidase IV Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs